During an immune response B-cells are stimulated to generate antibodies that specifically bind molecules that activate the immune system. The genetic recombination events involved with the synthesis of antibodies enables animals to create an immense diversity of antibodies each with its own characteristics such as binding specificity and binding affinity. Antibodies are currently being used for diverse diagnostic, imaging, or therapeutic applications. Antibodies that can be successfully used for diagnostic, imaging or therapeutic applications often require special characteristics. In particular, the kinetic properties of the antibody often dictate their utility. In general, the effectiveness or suitability of an antibody shows a strong positive correlation with the antibody's affinity for its target. As higher affinity antibodies are able to bind their target faster and remain bound to the target longer, they generally are effective at lower concentrations. Monoclonal antibodies (mAbs) can be generated by a variety of techniques including hybridoma technology, which involves fusing antibody-producing B-cells with cancerous mycloma cells. (Kohler & Milstein (1975) Nature 256: 52-53). The resulting hybridoma cell is an “immortalized” cell that secretes an antibody of single specificity (monoclonal antibody). An alternative method for monoclonal antibody generation is termed the Selected Lymphocyte Antibody Method (SLAM), described in U.S. Pat. No. 5,627,052 entitled “Methods for the production of proteins with a desired function” and in “A novel strategy for generating monoclonal antibodies from single, isolated lymphocytes producing antibodies of defined specificities” Babcook et al. (1996) Proc Natl Acad Sci USA. 93:7843-8. This method allows one to first identify B-cells that are making antibodies with desired characteristics such as binding specificity, function, and optimal kinetics. The selected B-cells are then isolated and the antibody variable domain genes encoding the binding portion of the antibody are rescued by molecular techniques, such as the polymerase chain reaction (PCR), and cloned into expression vectors having an antibody constant region domain. The expression vectors are then transfected into cells, such as CHO or NSO cells, to produce secreted antibody molecules. This process allows the virtually unlimited production of the desired antibody. Other methodologies such as phage display or the viral immortalization (including EBV) of B-cells have also been used successfully in the generation of monoclonal antibodies.
During the SLAM process, millions of B-cells are screened for the specificity, function and kinetic characteristics of the antibodies they produce. For a selected target, thousands of target-specific B-cells might be identified. Examples of known methods of screening include screening for antibodies which (1) bind to natively expressed antigen on the cell surface, (2) bind cell lines and induce apoptosis, (3) bind cells and either induce proliferation or block proliferation, and (4) bind to ligand and block binding of the ligand to receptor and vice versa. To determine formal affinity measurements of large panels of antibodies is a time-consuming, expensive, and inefficient process for identifying optimal antibodies. Accordingly, what is needed is a simple, rapid, and accurate mechanism for screening antibodies to determine their relative binding characteristics.